History
Sleep Disordered Breathing (SDB) and particularly Central Sleep Apnea (CSA) is a breathing disorder closely associated with Congestive Heart Failure (CHF). The heart function of patients with heart failure may be treated with various drugs, or implanted cardiac pacemaker devices. The breathing function of patients with heart failure may be treated with Continuous Positive Air Pressure (CPAP) devices or Nocturnal Nasal Oxygen. These respiratory therapies are especially useful during periods of rest or sleep. Recently, implanted devices to directly address respiration disturbances have been proposed. Some proposed therapeutic devices combine cardiac pacing therapies with phrenic nerve stimulation to control breathing.
Phrenic nerve pacing as a separate and stand alone therapy has been explored for paralyzed patients where it is an alternative to forced mechanical ventilation, and for patients with the most severe cases of central sleep apnea. For example, Ondine's Curse has been treated with phrenic nerve pacemakers since at least the 1970's. In either instance, typically, such phrenic nerve pacemakers place an electrode in contact with the phrenic nerve and they pace the patient's phrenic nerve at a constant rate. Such therapy does not permit natural breathing and it occurs without regard to neural respiratory drive.
Motivation for Therapy
SDB exists in two primary forms. The first is central sleep apnea (CSA) and the second is obstructive sleep apnea (OSA). In OSA the patient's neural breathing drive remains intact, but the pulmonary airways collapse during inspiration, which prevents air flow causing a form of apnea. Typically, such patients awake or are aroused as a result of the apnea event. The forced airflow of CPAP helps keep the airways open providing a useful therapy to the OSA patient.
CSA patients also exhibit apnea but from a different cause. These CSA patients have episodes of reduced neural breathing drive for several seconds before breathing drive returns. The loss of respiratory drive and apnea is due to a dysfunction in the patient's central respiratory control located in the brain. This dysfunction causes the patient's breathing pattern to oscillate between too rapid breathing called hyperventilation and periods of apnea (not breathing). Repeated bouts of rapid breathing followed by apnea are seen clinically and this form of disordered breathing is called Cheyne-Stokes breathing or CSR. Other patterns have been seen clinically as well including bouts of hyperventilation followed by hypopneas only.
In patients with CHF, prognosis is significantly worse when sleep apnea is present. A high apnea-hypopnea index (a measure of the number of breathing disturbances per hour) has been found to correlate to a poor prognosis for the patient. The swings between hyperventilation and apnea characterized by central sleep apnea have three main adverse consequences, namely: large swings in arterial blood gases (oxygen and carbon dioxide); arousals and shifts to light sleep; and large negative swings in intrathoracic pressure during hyperventilation. The large swings in blood gases lead to decreased oxygen flow to the heart, activation of the sympathetic nervous system, endothelial cell dysfunction, and pulmonary arteriolar vasoconstriction. Arousals contribute to increased sympathetic nervous activity, which has been shown to predict poor survival of patients with heart failure. Negative intrathoracic pressure, which occurs during the hyperventilation phase of central apnea, increases the after load and oxygen consumption of the left ventricle of the heart. It also causes more fluid to be retained in the patient's lungs. As a result of these effects the patient's condition deteriorates.
In spite of advances in care and in knowledge there is a large unmet clinical need for patients with sleep disordered breathing especially those exhibiting central sleep apnea and congestive heart failure.